Cyr61 is a product of immediate-early stress response gene existing in a variety of organs including lung. It has important roles in wound healing, angiogenesis, tumorigenesis, repair and remodeling. However, its role in pulmonary diseases has not been explored. The main hypothesis of this proposal is that Cyr61 has protective roles in hyperoxia induced acute lung injury. The central goal of this study is to define whether Cyr61 prevents lung epithelial cell death during lung injury induced by hyperoxia, and whether this molecule is involved in other cytoprotection pathways, such as heme oxygenase (HO-1 )/carbon monoxide (CO) pathway. The research design involves the studies at the cellular level and the animal level. The specific aims address the expression and regulation of Cyr61 under hyperoxia and/or carbon monoxide, effect of Cyr61 knocking down or over-expression on lung epithelial cell survival under hyperoxia, effect of specific over-expression of Cyr61 in lung on hyperoxia induced acute lung injury in animals, and potential roles of Cyr61 in CO mediated cytoprotection during lung injury. This study will provide novel information into the mechanisms of acute lung injury and repair, may form the basis for new therapeutic strategies.